Adjuvant therapy with aromatase inhibitors in postmenopausal, estrogen receptor- positive breast cancer patients: upfront or sequential?

For decades tamoxifen (TAM) has been the mainstay hormonal treatment for estrogen receptor positive (ER+) breast cancer patients. Nevertheless, during the last years, for postmenopausal women particularly, the third generation aromatase inhibitors (AI) became the preferred alternative. The results of the randomized trials showed that AI were superior to TAM in terms of efficacy, and were accompanied by a different but fairly convenient side effects profile. Subsequently, all updated guidelines recommend the use of AI in the adjuvant setting for this category of patients, either upfront, following 2-3 years of TAM or as extended adjuvant therapy, after 5 years of TAM. However, no consensus has been reached regarding the best strategy to be used, and the expert opinion is divided, based on the available evidence. The controversial aspect of whether AI should be used upfront or following 2-3 years of TAM is further detailed in this manuscript, and some useful recommendations are provided in order to facilitate the decision-making process during the current clinical practice.

Controversies around the use of monoclonal antibodies in the treatment of advanced non-small cell lung cancer.

First line combination chemotherapy (CT) using platinum-based doublets is established as a standard of care for advanced non-small cell lung cancer (NSCLC). Nevertheless, no significant advances have been recorded during the last years in this field. Therefore, there is a wide consensus among physicians that a plateau has already been reached with this strategy. Targeted therapy using tyrosine-kinase inhibitors (TKIs) and monoclonal antibodies emerged as a new field of development in the NSCLC therapeutics. Recently, the results of the phase III trials testing antibodies against vascular endothelial growth factor-VEGF (bevacizumab) and epidermal growth factor receptor-EGFR (cetuximab) challenged the paradigm of the platinum doublets as a gold standard in advanced NSCLC. Their appearance was enthusiastically commended both by patients and the oncological community. However, all medical oncologists have the responsibility to carefully analyze the real benefits of these new agents, to balance the advantages against the implicit risks of therapy and to make the decision having in mind the best interest of their patients. Last but not least, the associated health economic burden should also be considered. This paper addresses some issues related to the use of cetuximab and bevacizumab in advanced NSCLC. The main controversial aspects regarding patient selection, the real benefit of therapy, the molecular and clinical predictors, and the impact of other independent variables are carefully examined and presented. Due to many unsolved questions, no definite conclusions can be supported. The final decision about the optimal use of these agents is left to the clinical judgment of each treating physician.